Forty-five percent of deaths among children under 5 years of age are associated with undernutrition. Globally, almost 200 million children exhibit the two major forms of undernutrition—wasting (low weight-for-height) or stunting (low height-for-age), with many affected by both. Undernutrition is not due to food insecurity alone. Growing evidence indicates that perturbed postnatal gut microbiome development contributes to its pathogenesis. This perspective focuses on defining and repairing these defects in gut microbiome development. We describe an approach that involves the analysis of well-phenotyped human cohorts, followed by preclinical studies using gnotobiotic animals colonized with microbiota from these cohorts. Additionally, these models can be used to identify therapeutic targets and candidates that can then be tested clinically. Furthermore, introducing pretreatment microbiota from trial participants into gnotobiotic animals and re-enacting trial conditions allow mechanisms to be dissected. We highlight these recent advances as well as gaps in existing knowledge that present opportunities for future research.

Original languageEnglish
Pages (from-to)617-626
Number of pages10
JournalCell Host and Microbe
Issue number5
StatePublished - May 11 2022


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